GWAS of QRS duration identifies new loci specific to Hispanic/Latino populations

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Abstract
The electrocardiographically quantified QRS duration measures ventricular depolarization and conduction. QRS prolongation has been associated with poor heart failure prognosis and cardiovascular mortality, including sudden death. While previous genome-wide association studies (GWAS) have identified 32 QRS SNPs across 26 loci among European, African, and Asian-descent populations, the genetics of QRS among Hispanics/Latinos has not been previously explored. We performed a GWAS of QRS duration among Hispanic/Latino ancestry populations (n = 15,124) from four studies using 1000 Genomes imputed genotype data (adjusted for age, sex, global ancestry, clinical and study-specific covariates). Study-specific results were combined using fixed-effects, inverse variance-weighted meta-analysis. We identified six loci associated with QRS (P-8), including two novel loci: MYOCD, a nuclear protein expressed in the heart, and SYT1, an integral membrane protein. The top SNP in the MYOCD locus, intronic SNP rs16946539, was found in Hispanics/Latinos with a minor allele frequency (MAF) of 0.04, but is monomorphic in European and African descent populations. The most significant QRS duration association was with intronic SNP rs3922344 (P = 1.19x10-24) in SCN5A/SCN10A. Three other previously identified loci, CDKN1A, VTI1A, and HAND1, also exceeded the GWAS significance threshold among Hispanics/Latinos. A total of 27 of 32 previously identified QRS duration SNPs were shown to generalize in Hispanics/Latinos. Our QRS duration GWAS, the first in Hispanic/Latino populations, identified two new loci, underscoring the utility of extending large scale genomic studies to currently under-examined populations.
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  • National Institutes of Health (HL116747)
  • National Institutes of Health (HL111089)
  • Laughlin Family
  • National Heart, Lung, and Blood Institute (N01-HC65233)
  • National Heart, Lung, and Blood Institute (N01-HC65234)
  • National Heart, Lung, and Blood Institute (N01-HC65235)
  • National Heart, Lung, and Blood Institute (N01-HC65236)
  • National Heart, Lung, and Blood Institute (N01-HC65237)
  • National Heart, Lung, and Blood Institute (HHSN268201300024C)
  • National Institute of Dental and Craniofacial Research contracts (HHSN268201300005C AM03 and MOD03)
  • National Heart, Lung, and Blood Institute (HSN 26220/20054C)
  • National Center for Advancing Translational Sciences (UL1TR000124)
  • The National Institute of Diabetes and Digestive and Kidney Diseases (DK063491)
  • National Heart, Lung, and Blood Institute (T32HL7055)
  • National Heart, Lung, and Blood Institute (T32HL07779)
  • National Institutes of Health (R01HL124935)
  • National Institutes of Health (T32 HL139439)
  • National Heart, Lung, and Blood Institute (HL092217)
  • National Heart, Lung, and Blood Institute (HHSN268201500003I)
  • National Heart, Lung, and Blood Institute (N01-HC-95159)
  • National Heart, Lung, and Blood Institute (N01-HC-95160)
  • National Heart, Lung, and Blood Institute (N01-HC-95161)
  • National Heart, Lung, and Blood Institute (N01-HC-95162)
  • National Heart, Lung, and Blood Institute (N01-HC-95163)
  • National Heart, Lung, and Blood Institute (N01-HC-95164)
  • National Heart, Lung, and Blood Institute (N01-HC-95165)
  • National Heart, Lung, and Blood Institute (N01-HC-95166)
  • National Heart, Lung, and Blood Institute (N01-HC-95167)
  • National Heart, Lung, and Blood Institute (N01-HC-95168)
  • National Heart, Lung, and Blood Institute (N01-HC-95169)
  • National Heart, Lung, and Blood Institute (UL1-TR-000040)
  • National Heart, Lung, and Blood Institute (UL1-TR-001420)
  • National Heart, Lung, and Blood Institute (UL1-TR-001079)
  • National Heart, Lung, and Blood Institute (UL1-TR-001881)
  • National Heart, Lung, and Blood Institute (DK063491)
  • National Institutes of Health (DK073541)
  • National Institutes of Health (DK020595)
  • National Institutes of Health (AI085014)
  • National Institutes of Health (DK085501)
  • National Institutes of Health (HL102830)
  • National Institutes of Health (HHSN268200782096C)
  • National Institutes of Health (R01HL142302)
  • the National Heart, Lung, and Blood Institute (K23 HL136853)
  • Katz Foundation
  • National Heart, Lung, and Blood Institute (N02-HL-64278)
  • National Heart, Lung, and Blood Institute (HHSN268201600018C)
  • National Heart, Lung, and Blood Institute (HHSN268201600001C)
  • National Heart, Lung, and Blood Institute (HHSN268201600002C)
  • National Heart, Lung, and Blood Institute (HHSN268201600003C)
  • National Heart, Lung, and Blood Institute (HHSN268201600004C)
  • National Institutes of Health (T32HL007055)

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